{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T19:55:27Z","timestamp":1784404527330,"version":"3.55.0"},"reference-count":36,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,1,3]]},"abstract":"<jats:p>Tumor necrosis factor (TNF) and Fas ligand (FasL) play major roles in the homeostasis of the peripheral immune system. This becomes dramatically obvious in the absence of a functional FasL. Mice with such a deficiency develop a profound lymphadenopathy, splenomegaly, hypergammaglobulinemia, and strain-dependent systemic autoimmune disease, and succumb to premature death. It is consequently termed generalized lymphoproliferative disorder (gld). By contrast, TNF deficiency alone does not result in a striking phenotype. Thus, we sought to determine what role TNF might play in contributing to the gld phenotype by creating C57BL\/6.gld.TNF\u2212\/\u2212 mice. Contrary to the expected outcome, mice deficient for both FasL and TNF had a substantially milder gld phenotype with regard to mortality, lymphoaccumulation, germinal center formation, and hypergammaglobulinemia. To confirm these data in a strain highly permissive for the phenotype, C3H\/HeJ.gld and C3H.HeJ.lpr mice were treated with a TNF-specific monoclonal antibody. This transient neutralization of TNF also resulted in a significantly attenuated lymphoproliferative phenotype. We conclude that TNF is necessary for the full manifestation of the lymphoproliferative disorder, in particular playing a critical role in lymphoaccumulation. Most importantly, absence of TNF protects gld mice against premature death.<\/jats:p>","DOI":"10.1084\/jem.191.1.89","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:54Z","timestamp":1027702134000},"page":"89-96","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Tumor Necrosis Factor <b>Sustains the Generalized Lymphoproliferative Disorder (<\/b>\n                  <i>gld<\/i>\n                  <b>) Phenotype<\/b>"],"prefix":"10.1084","volume":"191","author":[{"given":"Heinrich","family":"K\u00f6rner","sequence":"first","affiliation":[{"name":"aFrom the Interdisziplin\u00e4res Zentrum f\u00fcr Klinische Forschung der Universit\u00e4t Erlangen-N\u00fcrnberg, D-91054 Erlangen, Germany"},{"name":"bInstitut f\u00fcr Klinische Mikrobiologie, Immunologie und Hygiene, D-91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Cretney","sequence":"additional","affiliation":[{"name":"dLaboratory of Cellular Cytoxicity, The Austin Research Institute, Heidelberg, 3084 Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Wilhelm","sequence":"additional","affiliation":[{"name":"aFrom the Interdisziplin\u00e4res Zentrum f\u00fcr Klinische Forschung der Universit\u00e4t Erlangen-N\u00fcrnberg, D-91054 Erlangen, Germany"},{"name":"bInstitut f\u00fcr Klinische Mikrobiologie, Immunologie und Hygiene, D-91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice M.","family":"Kelly","sequence":"additional","affiliation":[{"name":"dLaboratory of Cellular Cytoxicity, The Austin Research Institute, Heidelberg, 3084 Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"R\u00f6llinghoff","sequence":"additional","affiliation":[{"name":"bInstitut f\u00fcr Klinische Mikrobiologie, Immunologie und Hygiene, D-91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathon D.","family":"Sedgwick","sequence":"additional","affiliation":[{"name":"cDNAX Research Institute, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Smyth","sequence":"additional","affiliation":[{"name":"dLaboratory of Cellular Cytoxicity, The Austin Research Institute, Heidelberg, 3084 Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,1,3]]},"reference":[{"key":"2023072509002601500_R1","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/0092-8674(94)90372-7","article-title":"The TNF receptor superfamily of cellular and viral proteinsactivation, costimulation, and death","volume":"76","author":"Smith","year":"1994","journal-title":"Cell."},{"key":"2023072509002601500_R2","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/978-1-4899-0274-0_14","article-title":"The role of FasL and TNF in the homeostatic regulation of immune responses","volume":"406","author":"Lynch","year":"1996","journal-title":"Adv. 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